Pathophysiologic quantities of endotoxin-induced tumor necrosis factor-alpha release in whole blood from patients with chronic heart failure
Section snippets
Study population
We studied 15 patients with HF (aged 65 ± 1.9 years, New York Heart Association class 2.1 ± 0.3, left ventricular ejection fraction 31 ± 5%; mean ± SEM) and 7 healthy control subjects of similar age (mean age 59 ± 5 years; Table 1). The patients were recruited from the Royal Brompton Heart Failure Clinic (London, United Kingdom) and diagnosed with HF based on appropriate clinical signs and symptoms, together with objective evidence of reduced left ventricular function (ejection fraction <40%).
Study population
There were no significant differences between patients and controls in terms of age, height, weight, and body mass index (all p >0.05; Table 1). When patients were subgrouped into subjects with or without cardiac cachexia, body mass index was significantly lower in the subjects with cardiac cachexia (22.2 ± 1.7 vs 28.2 ± 4.1, p <0.002). There were no other significant differences between the 2 groups.
Whole blood stimulation
Patients with HF demonstrated elevated TNF-α release in response to stimulation by endotoxin
Discussion
We have shown that endotoxin, at pathophysiologic concentrations found in advanced and decompensated HF, induces the production of TNF-α in a dose-dependent manner in patients with mild and moderate HF. The confirmatory finding of elevated mRNA would suggest that de novo synthesis of TNF-α contributes, at least in part, to this finding. The release of sTNFR2, an important prognostic marker of survival, was likewise enhanced.
No previous study has evaluated the effects of low concentrations of
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